Mycotoxins and other fungal metabolites are thought to serve as chemical defense systems for the fungi that produce them and may also be of use in protecting the food source from consumption by other organisms [see: D. T. Wicklow, "Ecological Approaches to the Study of Mycotoxigenic Fungi," In Toxigenic Fungi--Their Toxins and Health Hazards, H. Kuvata et al. (eds.), Elsevier, New York, pp. 78-86 (1984)].
Roseotoxin B was isolated from extracts of a culture of Trichothecium roseum found on moldy corn by Richard et al. [Mycopathol. Mycol. Appl. 39: 231 (1969)]. Doses of purified roseotoxin B killed all test mice when injected intraperitoneally at 166 mg/kg; none of the mice died when given doses of 100 mg/kg [Richard et al., Mycopathol. Mycol. Appl. 40: 161 (1970)].
The structure of roseotoxin B was determined by Springer et al. [J. Am. Chem. Soc. 106 (8): 2388 (1984)]. As shown below, roseotoxin is a cyclic polypeptide in a class known as cyclodepsipeptides. It is closely related structurally to the destruxins which were isolated from Metarrhizium anisopliae. ##STR1##
Roseotoxin B differs from its closest relative in the destruxin series, destruxin A, in that the proline moiety in destruxin A is replaced by trans-3-methylproline in roseotoxin B.
Destruxins are substantially more toxic to mammals than roseotoxin B. Kodaira [Res. Repts. Fac. Textile Sericult., Shiushu University, No. 29, Ser. E, Agr. Sericult. No. 5: 1 (1961)] reported that intraperitoneal injections of 1.35 mg/kg of destruxin A caused the death of all mice tested. The mammalian toxicity of destruxin A is therefore approximately 100 times greater than that of roseotoxin B. Destruxin B killed all mice injected with 16.9 mg/kg and is about 10 times more toxic than roseotoxin B.
The destruxins have been found to possess insecticidal activity [Kodaira, supra]. In silk worm larvae injection of 0.28 .mu.g/g of destruxin A caused death while 0.34 .mu.g/g was required for destruxin B to produce the same effect; insecticidal activity in the destruxins appears to parallel toxicity to mammals. The destruxins were not effective as contact poisons and could not be tested as stomach poisons because feeding was severely inhibited. This phagodepressant effect was also noted for the larvae of potato lady beetle, Epilachma sparsa [Kodaira, supra] and Caravsius morosus [Roberts, In Naturally Occurring Insecticides, M. Jackson et al. (eds.), Marcel Dekker, Inc., New York, p. 509 (1971)].
Roberts [Proc. Joint U.S.-Japan Seminar Microbial Control Insect Pest, Fukuoka, 1967, p. 4 (1968)] also reported that the stick insect and a number of species of lepidoptera were susceptible to the destruxins. Mosquito larvae were killed by administration of 0.4 to 0.1 mg/larva in the culture water.
In addition to the destruxins, other classes of fungal mycotoxins such as aflatoxins and trichothecenes have been reported to be toxic to insects [see: V. F. Wright et al., "Mycotoxins and Other Fungal Metabolites as Insecticides," In Microbial and Viral Pesticides, E. Kurstak (ed.), Marcel Dekker, New York, pp. 559-583 (1982); S. Tamura et al., "Destruxins and Piericidins," In Naturally Occurring Insecticides, M. Jacobsen et al. (eds.), Marcel Dekker, New York, pp. 499-539 (1971). The roseotoxins, however, have not been previously reported to have insecticidal activity.